Purpose::
to study phenotype-genotype correlation in 65 consecutive patientswith retinoblastoma seen between March 2004 and January 2006and to report undescribed Rb1 mutations identified in patientsseen earlier.

Methods::
Complete ophthalmic examination was performed in all patientsand their parents. DNA was extracted from peripheral blood leucocytesand the Rb1 gene was screened by DHPLC and direct sequencingof the promoter and all the exons.

Results::
Thirty-two patients had bilateral retinoblastoma while thirty-threehad unilateral retinoblastoma. Overall, 29 mutations were foundin 65 patients (45 %). However, mutations were detected in 78%of the patients with bilateral retinoblastoma (25 out of 32patients) and only in 12% of the patients with unilateral retinoblastoma(4 out of 33 patients). Twenty-two mutations were single-basesubstitutions (76 %). Of these mutations 68% were of the nonsensetype (15 cases).Ten patients with bilateral retinoblastoma inwhom mutations were detected in a non-systematic approach between1995 and 1998 were added to our recent series. In total, tennovel mutations were identified, including 4 single base substitutions,4 small deletions and 2 small duplications. These are g.39445G>A,g.41924A>G, g.56851A>G, g.156795T>G, g.41983delT, g.44699_44706delAGCAGTTC,g.73788_73789delAA, g.78253delA, g.2157dupC and g.2179_2183dupGGACC.Two patients had dysmorphic features associated with 13q14 largedeletions.

Conclusions::
Low penetrance was observed in patients with the R661W mutations.All other mutations were associated with complete penetrance.As already reported, large deletions may be associated witha more severe syndromic form of retinoblastoma.